CN1862260B - Liquid delivery device and analysis system - Google Patents
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Abstract
本发明要解决的问题是,以前的用油充满的液体输送器件,在操作多个液体时,因其操作产生的油流动对其它液体产生影响。本发明的技术方案是,在液体输送器件中,用被空气分开的油滴包围输送的液体,进行操作。另外,作为接连不断地用油滴包围并处理多个液体的液体供给方法,由液体导入部使1个油滴和1个液滴相对应地供给,以生成被油滴包围的液体。若使用本发明,即使操作多个液体的情况下,也能不影响其它液体地稳定的操作。作为接连不断地被油滴包围的液体,可以在液体输送器件内处理,容易应用于分析系统中。
The problem to be solved by the present invention is that, when a conventional liquid conveying device filled with oil operates a plurality of liquids, the flow of oil generated by its operation affects other liquids. The technical solution of the present invention is that, in the liquid delivery device, the delivery liquid is surrounded by air-separated oil droplets for operation. In addition, as a liquid supply method in which a plurality of liquids are successively surrounded and treated with oil droplets, one oil droplet is supplied corresponding to one liquid droplet from the liquid introduction part to generate a liquid surrounded by oil droplets. According to the present invention, even when handling a plurality of liquids, it is possible to operate stably without affecting other liquids. As a liquid continuously surrounded by oil droplets, it can be handled in the liquid delivery device and easily applied in the analysis system.
Description
技术领域technical field
本发明涉及在基片上操作液体的系统。特别涉及输送许多液体的分析或反应系统。The present invention relates to systems for manipulating liquids on substrates. It is especially concerned with analytical or reaction systems where many liquids are transported.
背景技术Background technique
作为检测试样中所包含的成分量的分析装置,广泛使用了光谱分析装置,它是通过将从卤灯等发出的白色光照射到作为试样与试剂的混合液的反应液上,用衍射光栅对透过了反应液的光进行分光,通过取出必要的波长成分,并算出其吸光度来测定目标成分量。或者,也有用衍射光栅对白色光进行分光之后,再照射到反应液上的情况。在这些分析装置中,以前是将)试样和试剂分注到塑料和玻璃的反应容器内,将它们混合成为反应液并对其照射光,以测定成分量。As an analysis device for detecting the amount of components contained in a sample, a spectroscopic analysis device is widely used, which is to irradiate white light emitted from a halogen lamp etc. The grating splits the light transmitted through the reaction solution, extracts necessary wavelength components, and calculates the absorbance to measure the amount of the target component. Alternatively, white light may be irradiated onto the reaction solution after being separated by a diffraction grating. In these analytical devices, conventionally, a sample and a reagent are dispensed into a plastic or glass reaction container, and they are mixed to form a reaction solution, which is irradiated with light to measure the amount of the component.
可是,近年来,为了削减试剂成本和降低对环境的负荷,要求分析所用的反应液的微量化,存在的问题是,对于以现有方式实现反应液的微量化来说,反应液的操作变得困难,而且,因分注、混合时产生的气泡等而不能正确地测定。因此,要求正确操作微量液体的技术。However, in recent years, in order to reduce the cost of reagents and reduce the load on the environment, it is required to reduce the amount of the reaction solution used in the analysis, and there is a problem that the operation of the reaction solution is changed when the amount of the reaction solution is reduced by the conventional method. It is difficult to obtain, and it cannot be accurately measured due to air bubbles generated during dispensing and mixing. Therefore, techniques for correctly handling minute amounts of liquid are required.
作为操作微量液体的一个方法,有用电控制输送在平面基片所形成的电极上的液体的方法。这种方法的代表之一是,通过在形成了多个电极的两个相对的基片间,把输送的液体做成粒状液体并夹住,对沿两个相对的基片间的表面配置的电极施加电压,由此输送液体。(例如,非专利文献1-AppliedPyhysics Letters,Vol,77,No.11,pp.1725-1726,2000,非专利文献2-IEEE15th,Int.Conf.MEMS Jan 2002,p.97-100.)。将由两个相对的基片构成的装置称为液体输送器件。对于该方法,通常,沿着输送液体的液体输送通道,在一个基片上形成多个电极,在另一个基片上还具有与地面连接的一个电极。当对粒状的液体下部的一个电极施加电压时,根据电湿润现象(例如,非专利文献3-Polymr 37(1996)2465-2470),施加了电压的电极上的润湿性变得良好,其粒状液体移动使其载置于施加了该电压的电极上。通过反复这样做来输送液体。As one method of handling a minute amount of liquid, there is a method of electrically controlling the liquid transported on electrodes formed on a planar substrate. One of the representatives of this method is, by forming the liquid that is transported into a granular liquid between two opposing substrates with a plurality of electrodes and sandwiching it, the electrodes disposed along the surface between the two opposing substrates The electrodes apply a voltage, thereby transporting the liquid. (For example, Non-Patent Document 1-Applied Pyhysics Letters, Vol, 77, No.11, pp.1725-1726, 2000, Non-Patent Document 2-IEEE15th, Int. Conf. MEMS Jan 2002, p.97-100.). A device consisting of two opposing substrates is referred to as a liquid transport device. For this method, generally, a plurality of electrodes are formed on one substrate along a liquid delivery path through which the liquid is delivered, and an electrode connected to the ground is also provided on the other substrate. When a voltage is applied to an electrode in the lower part of the granular liquid, according to the electrowetting phenomenon (for example, non-patent document 3-Polymr 37 (1996) 2465-2470), the wettability on the electrode to which the voltage is applied becomes good, which The granular liquid moves to be placed on the electrode to which the voltage is applied. The fluid is delivered by doing this repeatedly.
另外,还报告了用具有多个分支的电极列把液体分配给分支,或在多个槽合流的位置使液体汇合(例如,专利文献1-日本特开平10-267801号公报)。另外,还报告了分割一个粒状的液体的情况(例如,专利文献2-美国专利公报第6565727号公报)。而且,还报告了输送试样,在液体输送器件内部进行检测那样的系统(例如,非专利文献4-Micro Total Analysis Systems2003 p.1287-1290)。In addition, it is also reported that liquid is distributed to branches using an electrode array having a plurality of branches, or that liquids are merged at a position where a plurality of grooves join (for example, Patent Document 1 - Japanese Patent Application Laid-Open No. 10-267801). In addition, a case where a single granular liquid is divided is also reported (for example, Patent Document 2 - US Patent Publication No. 6565727). In addition, a system that transports a sample and detects it inside a liquid transport device has also been reported (for example, non-patent document 4-Micro Total Analysis Systems 2003 p.1287-1290).
这样的输送液体的液体输送器件的优点可以列举,与周围被壁包围的容器比较,由于利用基片,所以难以受到气泡的影响等。这里,对充满液体输送器件内部的介质报告有二种。一种如非专利文献1记载的那样,是用油充满内部的情况,另一种如非专利文献2记载的那样,是用空气充满内部的情况。Advantages of such a liquid transport device for transporting liquid include that, compared with a container surrounded by walls, it is less affected by air bubbles due to the use of a substrate. Here, there are two kinds of reports on the media filling the interior of the liquid delivery device. One is a case where the inside is filled with oil as described in
另一方面,作为自动分析装置的液体输送方法,具有将水溶液段导入到容纳有硅油等液体的导管中并进行输送的报告(例如,专利文献3-美国专利公报第3479141号公报)。关于抽吸、分注已分离的液体或在液流中输送的装置,有用空气段和不混合性液体段相互间隔开来输送多个试样段的报告(例如,专利文献4-美国专利公报第4259291号公报)。On the other hand, as a liquid transport method for an automatic analyzer, there is a report of introducing and transporting an aqueous solution segment into a conduit containing a liquid such as silicone oil (for example, Patent Document 3 - US Patent Publication No. 3479141). With regard to devices for aspirating, dispensing separated liquids, or conveying in a liquid stream, there are reports of delivering multiple sample segments with air segments and immiscible liquid segments spaced apart from each other (for example, Patent Document 4 - U.S. Patent Gazette Bulletin No. 4259291).
而且,还有用油的液滴包围液体,利用电湿润现象进行输送(非专利文献 5-Lab-on-a-Chip:Platforms Devices,and Applications,Conf.5591,SPIEO Ptics East,Philadelphia,Oct.25-28,2004)的报告。Moreover, there is also a liquid surrounded by oil droplets, which is transported by electrowetting (non-patent literature 5-Lab-on-a-Chip: Platforms Devices, and Applications, Conf.5591, SPIEO Ptics East, Philadelphia, Oct.25 -28, 2004) report.
在用油充满液体输送器件内的情况下,由于输送的粒状液体用油包围,因而具有液体输送器件的表面难以带来污染、液体和液体输送器件的摩擦因油而降低并使移动所需要的电压下降、可防止液体的蒸发等优点。但是,需要密封液体输送器件的底面和侧面,以使其不泄漏油,安装也很费工夫。要考虑的问题是,在操作液体时油产生流动,使其它液体受到影响。例如,在将液体导入液体输送器件内时,要考虑的问题是,分注液体的测管和被导入的粒状液体在油中产生流动,使配置在液体输送器件内的其它液体移动等。在液体无控制地移动的情况下,有和其它液体接触并混合或液体脱离液体输送通道而不能输送的可能性。特别是在分析系统中,需要对多数的试样和试剂,实行分注、输送、混合、检测、排出等对多种液体的许多操作。因此,重要的是,对某种液体的操作不要造成对其它液体的影响。In the case of filling the inside of the liquid delivery device with oil, since the conveyed granular liquid is surrounded by oil, the surface with the liquid delivery device is less likely to be polluted, the friction between the liquid and the liquid delivery device is reduced by the oil and the movement required Voltage drop, can prevent the evaporation of liquid and other advantages. However, it is necessary to seal the bottom surface and the side surface of the liquid conveying device so that oil does not leak, and installation is also labor-intensive. The problem to be considered is that when the liquid is manipulated, the oil will flow and other liquids will be affected. For example, when a liquid is introduced into a liquid delivery device, problems to be considered are that the measuring tube for dispensing the liquid and the introduced granular liquid flow in the oil and move other liquids arranged in the liquid delivery device. Where the liquid moves uncontrollably, there is a possibility that it will come into contact with and mix with other liquids or that the liquid will break away from the liquid delivery channel and cannot be delivered. Especially in an analysis system, it is necessary to perform many operations for various liquids, such as dispensing, transporting, mixing, detecting, and discharging, for many samples and reagents. Therefore, it is important that operations on one liquid do not affect other liquids.
另外,在考虑向在液体输送器件内进行检测的分析系统的应用的情况下,要考虑的问题是,从导入液体的导入口使气泡进入到油中时,气泡在测定部妨碍了测定等。与此相反,在用空气充满了液体输送器件内的情况下,由于无需密封液体输送器件的底面和侧面,安装是容易的;而且,由于液体周围是空气,因而,对某液体的操作不会对其它液体产生影响,具有能对许多液体独立稳定地进行操作的优点。但是,与用油包围的情况不同,由于液体直接接触到液体输送器件的表面,因而,要考虑的问题是,液体内部成分易于吸附,或者,因液体和液体输送器件的摩擦较大而使移动所需要的电压增高,不能防止液体的蒸发等。在使用了液体输送器件的分析系统中,为了测定作为输送的液体的试样内部成分的浓度,重要的是防止液体内部成分的吸附和蒸发。In addition, when considering application to an analysis system for detection in a liquid transport device, there is a problem that when air bubbles enter the oil from an inlet for introducing liquid, the air bubbles interfere with measurement in the measurement section. On the contrary, in the case of filling the liquid delivery device with air, since there is no need to seal the bottom and side surfaces of the liquid delivery device, installation is easy; and since the liquid is surrounded by air, the operation of a certain liquid will not Effects on other liquids have the advantage of being able to operate independently and stably on many liquids. However, unlike the case of being surrounded by oil, since the liquid directly contacts the surface of the liquid delivery device, it is considered that the internal components of the liquid are easily adsorbed, or that the friction between the liquid and the liquid delivery device is relatively large and causes movement. The required voltage increases, and evaporation of the liquid, etc., cannot be prevented. In an analysis system using a liquid transport device, in order to measure the concentration of a component in a sample as a liquid to be transported, it is important to prevent adsorption and evaporation of components in the liquid.
在利用不与输送的液体混合的输送用液体的液滴包围输送的液体,并与输送的液体一起输送输送用液体的方式中,有必要适当地用输送用液体进行包围。一般的分析系统虽有必要接连不断地检测多个试样,但在利用该输送方式多次检测试样时,为了防止试样的污染和提高检测的效率,有必要适当而简便地进行该包围。In an embodiment in which the liquid to be transported is surrounded by droplets of the liquid for transport that do not mix with the liquid to be transported, and the liquid for transport is transported together with the liquid to be transported, it is necessary to surround the liquid for transport appropriately. Although it is necessary for a general analysis system to continuously detect multiple samples, when using this transport method to detect multiple samples, in order to prevent contamination of the sample and improve the efficiency of detection, it is necessary to properly and easily perform this encirclement. .
发明内容Contents of the invention
本发明的目的在于提供一种兼具有这些用油充满的情况和用空气充满的情况的优点,安装简易,能稳定地输送许多液体,液体内部的成分难以吸附,能降低移动所需要的电压,而且能防止试样蒸发的液体输送器件,以及接连不断地与输送用液体一起输送许多试样的分析系统。The object of the present invention is to provide a device that has both the advantages of filling with oil and filling with air, is easy to install, can stably transport many liquids, is difficult to absorb the components inside the liquid, and can reduce the voltage required for movement. , and a liquid delivery device that can prevent the sample from evaporating, and an analysis system that continuously transports many samples together with the delivery liquid.
本发明提供的液体输送器件采用分开的输送用液体包围输送的液体,与输送的液体一起对输送用液体进行输送。因此,其安装简易,可以稳定地输送多个液体,液体内部的成分难以吸附,从而可以降低移动所需要的电压,能防止试样的蒸发。本发明提供的分析系统把输送的液体依次导入到与输送的液体不混合的被分开的输送用液体中,以接连不断地与输送的液体一起输送输送用液体。The liquid transporting device provided by the present invention adopts separate transporting liquids to surround the transporting liquid, and together with the transporting liquid, transports the transporting liquid. Therefore, it is easy to install, can transport multiple liquids stably, and the components inside the liquid are difficult to absorb, so that the voltage required for movement can be reduced, and the evaporation of the sample can be prevented. The analysis system provided by the present invention sequentially introduces the transported liquid into the separated transported liquid which is not mixed with the transported liquid, so as to continuously transport the transported liquid together with the transported liquid.
作为分析系统的一个例子,其具有:具备供给第一液体的部件和供给第二液体的部件的第一单元;具备从供给上述第一液体的部件导入上述第一液体的第一导入部,用于排出上述第一液体的排出部,具有多个电极而且连接上述导入部和上述排出部的液体输送通道,设置在上述液体输送通道的至少一部分上的测定部和对上述多个电极的至少一部分施加电压的电压施加部件的第二单元;具备检测上述测定部的检测系统的第3单元;用于从上述排出部排出液体的第4单元;其特征是,上述第二液体是和上述第一液体不混和的,上述第一单元将上述第二液体分开并供给上述第二单元,从而使其内包被分开的第一液体,上述电压施加部件对上述多个电极的至少一部分施加电压,从而使被分开的第一液体与内包上述被分开的第一液体且被分开的第二液体的复和体沿上述液体输送通道移动。As an example of an analysis system, it has: a first unit provided with a part for supplying the first liquid and a part for supplying the second liquid; a first introduction part for introducing the first liquid from the part for supplying the first liquid; In the discharge part that discharges the above-mentioned first liquid, there is a liquid delivery channel that has a plurality of electrodes and connects the above-mentioned introduction part and the above-mentioned discharge part, a measurement part provided on at least a part of the above-mentioned liquid delivery channel, and at least a part of the plurality of electrodes. A second unit of a voltage applying member for applying a voltage; a third unit having a detection system for detecting the above-mentioned measuring part; a fourth unit for discharging liquid from the above-mentioned discharge part; it is characterized in that the above-mentioned second liquid is the same as the above-mentioned first If the liquids are immiscible, the first unit divides the second liquid and supplies it to the second unit so that the separated first liquid is contained therein, and the voltage applying part applies a voltage to at least a part of the plurality of electrodes, so that A complex of the divided first liquid and the divided second liquid including the divided first liquid moves along the liquid transport path.
作为分析系统的另一个例子,其具有:具备供给第一液体的部件和供给第二液体的部件的第一单元;具备从供给上述第一液体的部件导入上述第一液体的第一导入部,从供给上述第二液体的部件导入上述第二液体的第二导入部,用于排出上述第一液体的排出部,具有多个电极而且连接上述第一导入部和上述排出部的液体输送通道,设置在上述液体输送通道的至少一部分上的测定部和对上述多个电极的至少一部分施加电压的电压施加部件的第二单元;具备与上述测定部相邻地配置的检测系统的第3单元;用于从上述排出部排出液体的第4单元;其特征是,上述第二液体是与上述第一液体不混和的,供给上述第一液体的部件分开地送出上述第一液体,供给上述第二液体的部件分开地送出上述第二液体,上述电压施加部件对上述多个电极的至少一部分施加电压,从而使由供给上述第一液体的部件分开的第一液体从上述第一导入部沿上述液体输送通道向上述第二导入部移动,而且使由导入到上述第二导入部的第二液体的至少一部分内包的第一液体沿上述液体输送通道移动。As another example of the analysis system, it has: a first unit having a part for supplying the first liquid and a part for supplying the second liquid; a first introduction part for introducing the first liquid from the part for supplying the first liquid, A second introduction part for introducing the second liquid from the part for supplying the second liquid, a discharge part for discharging the first liquid, a liquid delivery channel having a plurality of electrodes and connecting the first introduction part and the discharge part, A second unit comprising a measurement unit provided on at least a part of the liquid transport channel and a voltage applying member for applying a voltage to at least a part of the plurality of electrodes; a third unit including a detection system disposed adjacent to the measurement unit; A fourth unit for discharging liquid from the discharge part; characterized in that the second liquid is immiscible with the first liquid, and the part for supplying the first liquid separately sends the first liquid and supplies the second liquid. The liquid part sends out the second liquid separately, and the voltage applying part applies a voltage to at least a part of the plurality of electrodes, so that the first liquid separated by the part for supplying the first liquid flows along the liquid from the first introduction part. The transfer channel moves toward the second introduction part, and moves the first liquid contained in at least a part of the second liquid introduced into the second introduction part along the liquid transfer channel.
若使用本发明,与以前的用油充满的液体输送器件比较,安装简易,液体不会因分注和输送等的液体操作产生的油流动而无控制地移动,能对许多液体进行稳定而独立的操作。另外,能把由已分开的油滴包围的液体接连不断地导入到液体输送器件中,能提高处理许多试样的分析系统的效率。If the present invention is used, compared with the previous liquid delivery device filled with oil, it is easy to install, the liquid will not move uncontrollably due to the oil flow generated by the liquid operation such as dispensing and transportation, and it can stably and independently carry out many liquids. operation. In addition, the liquid surrounded by the separated oil droplets can be continuously introduced into the liquid delivery device, which can improve the efficiency of an analysis system that processes many samples.
附图说明Description of drawings
图1是表示本发明实施例1的液体输送器件的液体输送通道的剖面图。Fig. 1 is a sectional view showing a liquid transfer channel of a liquid transfer device according to
图2是说明本发明实施例1的液体输送顺序的略图。Fig. 2 is a schematic diagram illustrating the liquid delivery sequence in
图3是表示本发明实施例1的其它结构的液体输送通道的剖面图。Fig. 3 is a cross-sectional view showing another structure of a liquid transfer channel according to
图4是表示本发明实施例1的其它结构的液体输送通道的剖面图。Fig. 4 is a cross-sectional view showing another structure of a liquid transfer channel according to
图5是表示本发明实施例1的其它结构的液体输送通道的剖面图。Fig. 5 is a cross-sectional view showing another structure of a liquid transfer channel according to
图6是表示本发明实施例1的其它结构的液体输送通道的剖面图。Fig. 6 is a cross-sectional view showing another structure of a liquid transfer channel according to
图7是表示本发明的液体输送器件内的速度比较图。Fig. 7 is a graph showing the speed comparison in the liquid transport device of the present invention.
图8是输送包含本发明实施例1的油中所存在的物质的液体的说明图。Fig. 8 is an explanatory diagram for transporting a liquid containing substances present in oil of Example 1 of the present invention.
图9是说明本发明实施例2的略图。Fig. 9 is a schematic
图10是说明本发明实施例2的略图。Fig. 10 is a schematic
图11是说明本发明实施例2的略图。Fig. 11 is a schematic
图12是说明本发明实施例2的略图。Fig. 12 is a schematic
图13是说明本发明实施例3的略图。Fig. 13 is a schematic
图14是说明本发明实施例4的略图。Fig. 14 is a schematic
图15是说明本发明实施例4的略图。Fig. 15 is a schematic
图16是说明本发明实施例5的分析系统的略图。Fig. 16 is a schematic diagram illustrating an analysis system of
图17是表示使用本发明的分析系统时的液体输送器件内的操作顺序图。Fig. 17 is a diagram showing the sequence of operations in the liquid transport device when the analysis system of the present invention is used.
图18是本发明的液体输送器件内的各部分的配置图。Fig. 18 is a layout diagram of various parts in the liquid delivery device of the present invention.
图19是本发明的液体输送器件的外观图。Fig. 19 is an external view of the liquid delivery device of the present invention.
图20是本发明的控制系统的略图。Fig. 20 is a schematic diagram of the control system of the present invention.
图21是本发明的实施例5的试样导入口的断面图。Fig. 21 is a cross-sectional view of a sample introduction port in Example 5 of the present invention.
图22是本发明的实施例5的试样导入口的断面图。Fig. 22 is a cross-sectional view of a sample introduction port in Example 5 of the present invention.
图23是本发明的实施例5的试剂导入口的断面图。Fig. 23 is a sectional view of a reagent inlet in Example 5 of the present invention.
图24是本发明的实施例5的测定部的断面图。Fig. 24 is a cross-sectional view of a measurement unit in Example 5 of the present invention.
图25是本发明的实施例5的测定部的断面图。Fig. 25 is a cross-sectional view of a measurement unit in Example 5 of the present invention.
图26是本发明的实施例5的排出口的断面图。Fig. 26 is a sectional view of a discharge port according to
图27是本发明的实施例5的排出口的断面图。Fig. 27 is a cross-sectional view of a discharge port according to
图28是说明本发明的实施例6的略图。Fig. 28 is a schematic
图29是说明本发明的实施例5的略图。Fig. 29 is a schematic
图30是说明本发明的实施例7的略图。Fig. 30 is a schematic
图31是说明本发明的实施例7的略图。Fig. 31 is a schematic
具体实施方式Detailed ways
实施例1Example 1
本实施例表示在液体输送器件内,用油滴作为输送用液体的液滴,输送被油滴包围的液体的顺序。图1表示本实施例的液体输送器件10的液体输送通道的剖面结构图。液体输送器件10由下侧基片8和上侧基片9构成。下侧基片8在绝缘基片4的上表面沿液体(油滴)1的输送方向配置多个控制电极5,并用绝缘膜7覆盖其表面。上侧基片9在绝缘基片4’的下表面配置一个共用电极6,并用绝缘膜7’覆盖其表面。进而,在各自的绝缘膜7、7’的表面上,为了易于输送液体而使其具有疏水性,在表面涂敷疏水膜100、100’。在这两个基片间配置输送的液体1,用油滴2包围其周围。即,输送的液体1被油滴2包在内部,成为液体1的液滴和油滴2的复合体。这里,所谓包在内部是指,一个油滴处于实质上覆盖一个液滴(液体)的外表面的位置。油滴2的周围存在空气3。This embodiment shows a procedure for transporting a liquid surrounded by oil droplets using oil droplets as droplets of the transport liquid in the liquid transport device. FIG. 1 shows a cross-sectional view of the liquid delivery channel of the
在本实施例中,绝缘性基片4、4’用石英,控制电极5及共用电极6用銦-氧化锡(ITO-Indium-TinOxide),绝缘膜7、7’用由化学气相淀积(CVD-Chemi Vapor Deposition)成膜的SiO2,作为疏水膜用旭硝子社制的CYTOP(注册商标)。ITO的厚度设为70nm,由CVD成膜的绝缘膜7的厚度设为200nm。另外,下侧基片8和上侧基片9之间的距离设为0.5mm。作为液体1用0.9wt%的NaCl溶液,作为油滴2用硅油,液量各自为5μL。通过在下侧基片8和上侧基片9之间设置用油滴包围的液体,从而提高防止油蒸发的效果,还能避免油因重力拉引而与液体分离。In this embodiment, the insulating
图2表示从上部看本实施例使用的液体输送器件的透视图。为了简略化便于理解,本申请中,在图2及图8-图15的透视图中仅图示液体1、油滴2、控制电极5,用阴影线表示施加电压的控制电极。位于控制电极5上部的共用电极6与地连接,电压施加在共用电极6和一部分控制电极5之间。本申请中,没有施加电压的控制电极5成为不与任何地方连接的浮动状态,在切断施加电压的情况下,停止施加电压后一旦把控制电极5与地连接后,控制电极5变成浮动状态。因此,在切断施加电压时,就能防止控制电极上的绝缘膜和疏水膜成为局部带电的状态。在共用电极6和控制电极5之间施加电压的情况下,从上部看,具有与控制电极5一部分重叠的区域的液体1便移动而呈置于施加了电压的控制电极5上的状态,即,液体如置于施加了电压的控制电极5上的状态移动。开始,如图2(a)所示,沿液体输送通道配置多个控制电极5,在控制电极5b的附近存在被油滴2包围的液体1时,对控制电极5b一施加电压,如图2(b)所示,液体1则移动使其置于控制电极5b上。Fig. 2 shows a perspective view from above of the liquid delivery device used in this embodiment. For the sake of simplification and ease of understanding, in this application, only the
接着,当对控制电极5c施加电压,切断控制电极5b的施加电压时,如图2(c)所示,液体1与油滴2和空气3的气液界面接触后,一边挤压油滴2和空气3的气液界面,一边如图2(d)那样与油滴2一起移动,移动到置于控制电极5c上。进而,当对控制电极5d施加电压,切断控制电极5c的施加电压时,液体1如图2(e)那样一边挤压油滴2和空气3的气液界面,一边如图2(f)那样与油滴2一起移动,移动到置于控制电极5d上。通过这样的反复,能使液体1在被油滴2包围的状态下输送。并且,被油滴2包围的液体1等于沿控制电极的排列移动。如本实施例所示,通过用输送用液体包围液体,能防止输送的液体的内部成分向基片表面的吸附,而且能防止液体的蒸发。进而,由于液体1和液体输送器件10的摩擦小,与用空气充满液体输送器件内的情况比较,即使是低电压也能输送液体。对控制电极施加的电压过高时,由于有破坏绝缘膜的危险,降低电压是有用的。由于用油滴2作为输送用液体被分开隔开,因而,不会将输送液体1引起的油流动传递给其它液体,能稳定独立地对液体输送器件内的许多液体进行操作。Next, when a voltage is applied to the
在本实施例中,作为液体1碎使用NaCl溶液,但也可以是纯水、缓冲液等离子性液体。也可以是血液和含有DNA的溶液。也可以在液体中含有胶乳粒子、细胞、磁性小珠。作为油滴2虽使用硅油,但也可以是植物油、石腊油、杜邦公司制的Krytox(注册商标)等的氟系列油、氟系列溶剂等与输送的液体不混合的液体、即不混和的液体。作为绝缘性基片4、4’虽使用石英,但也可以是在Si等的导电性基片上形成了氧化膜等绝缘膜的基片或树脂性基片。绝缘膜7、7’虽使用由CVD法成膜的SiO2,但也可以是聚硅氮烷或SiN,聚对亚苯基二甲基(Parylene)等绝缘膜。作为疏水膜100、100’虽使用旭硝子社制的CYTOP,但也可以是杜邦公司制的TeflonAF(注册商标)或硅系列疏水膜、CVD法成膜的碳氟化合物膜(CF(Fluorocarbon film)膜)。In this embodiment, NaCl solution was used as the liquid, but ionic liquids such as pure water and buffer solutions may also be used. It can also be blood and solutions containing DNA. It is also possible to contain latex particles, cells, magnetic beads in the liquid. Although silicone oil is used as the
在本实施例中,虽在绝缘膜上形成了疏水膜,但也可以是疏水性绝缘膜或绝缘性疏水膜。这种情况由于工序减少,使器件制作变得简易。在本实施例中,共用电极6虽为一个,但如图3所示,也可以在上侧基片9上配置多个共用电极6。在这种情况下,具有在输送时提高液体的位置精度的效果。在本实施例中,虽然分别用绝缘膜7、7’覆盖控制电极5及共用电极6,但如图4所示,也可以用绝缘膜7覆盖控制电极5的表面,在共用电极6的表面没有绝缘膜7’。这时能作成简单的结构。再有,也可以在共用电极6的表面不涂敷疏水膜100、100’。这时,能作成更简单的结构。In this embodiment, although the hydrophobic film is formed on the insulating film, it may be a hydrophobic insulating film or an insulating hydrophobic film. In this case, since the number of steps is reduced, device fabrication becomes easier. In this embodiment, one
如图5所示,预先在下侧基片8的控制电极5之间配置共用电极6等,在上侧基片9的表面上不配置共用电极6,在下侧基片8设置多个电极,则可以将该多个电极中的任一个作为控制电极5,而将另外的任一个作为共用电极6。这时,由于不需要在上侧基片上形成电极膜,因而其结构更简单。再有,也可以在上侧基片9的绝缘性基片4’表面不涂敷疏水膜。这时,可制成更简单的结构。另外,如图6所示,也可以不设置上侧基片9,只采用下侧基片8的结构进行输送。这时的结构进一步简化。As shown in Figure 5, the
在本实施例中,虽然水平配置构成液体输送器件10的下侧基片8、上侧基片9,但也可以使下侧基片8、上侧基片9的一部分面或整个面与水平方向成一大定角度地配置。在以前的用油充满的液体输送器件中,当与水平方向形成角度时,就会出现漏油的情况,但若使用本发明,由于油利用二块水平基片保持,油难于流动,可以与水平方向形成角度。若能与水平方向形成角度,则能缩小整个装置的设置面积,是有用的。另外,本实施例虽使用硅油包围液体1的周围,但也可以进一步用氟系列油或氟系列溶剂包围该硅油的周围。In this embodiment, although the
接着,比较被油滴2包围的液体1一边挤压油滴2的气液界面,一边被输送的油滴输送,以及液体1的周围是空气时的空气内输送的速度。图7表示液体1相对各种情况的电压变化的速度变化。在油滴输送的情况下,从20V就能输送液体,但在空气内输送的情况下,20V则不能输送液体,要从40V才能输送液体,由此可知能降低输送所需要的电压。这可以认为是因为液体1和液体输送器件表面之间加入油,减轻了摩擦之故。对电极施加的电压过高时,由于有破坏绝缘膜的危险,所以降低用于输送液体的电压是有用的。Next, the transport speed of the oil droplet transported while the
使用图8说明与液体同时输送包含在油滴中的物质的情况。如图8(a)所示,在液体输送通道中的一个油滴2中存在两个液体(液滴,以下同样)1a、1b时,如图8(b)所示,当对控制电极5e施加电压时,只有具有与控制电极5e重叠区域的液体1b移动到控制电极5e上。这时,液体1a挤压油滴2的油和空气的气液界面,如图8(c)所示与液体1b一起输送。进而,如图8(d)所示,当对控制电极5f施加电压,切断控制电极5e的施加电压时,液体1b移动到控制电极5f上,液体1a也挤压油和空气的气液界面并移动。在油滴2中有两个以上的液体时也能同样地移动。像以上那样做,在在油滴2中有多个液体(液滴)的情况下,施加电压的液滴以外的液滴也能通过挤压油滴的气液界面而一起移动。因此,同时输送两个以上的液体的情况下,利用同样的油滴包围,只要控制一个液体即可,液体的控制变得容易。The case where the substance contained in the oil droplet is transported simultaneously with the liquid will be described using FIG. 8 . As shown in Figure 8(a), when there are two liquids (droplets, hereinafter the same) 1a, 1b in one
在本实施例中,作为油滴2中的物质,虽以与施加电压的液体不同的液体为例,但只要是被油滴2包含的物质即可,即使是粒子等固体也能同样地移动。通常,油虽不能在液体输送器件内控制输送,但使用本发明,通过输送作为油滴被油包含的液体,能把油移动到预定的位置。因此,通过移动、混合许多油也能使被油包含的物质反应。In this embodiment, as the substance in the
实施例2Example 2
本实施例表示混合被油滴包围的两个液体等的顺序。以下分为合体(合成一体)和搅拌说明混合的顺序。This example shows the sequence of mixing two liquids, etc., surrounded by oil droplets. The following is divided into combination (synthesis) and stirring to explain the mixing order.
如图9(a)那样,在控制电极5上配置被油滴2a包围的液体(液滴)1a和被油滴2b包围的液体1b时,对位于两个液体(液滴)之间且各个液滴的一部分分别重叠着的控制电极5a、5b施加控制电压时,如图9(b)那样,使液体(液滴)1a、1b移动到置于各自的一部分重叠的控制电极上。接着,对如图9(c)那样配置在两个液体(液滴)之间的控制电极、进而是两个液体(液滴)移动目的地的、配置在控制电极5b、5d之间的控制电极5c施加电压,切断向作为与控制电极5c相邻的控制电极的控制电极5b、5d的施加电压。因此,两个液体的液滴就要移动到控制电极5c上;如图9(d)那样油2a、油2b合体后,如图9(e)那样液体1a、液体1b合体,成为一个被油包围的液体1。通过像本实施例那样合体的液体被油滴包围,因合体产生的油的流动不会传播到合体的液体以外的液体中,能稳定而独立地操作液体输送器件内的许多液体。As shown in Figure 9 (a), when the liquid (droplet) 1a surrounded by the
接着,表示搅拌被油滴包围的液体成分的顺序。图10表示搅拌液体1的控制电极的配置图。如图10所示,油滴2中的液体1位于实质上以直线状配置的多个电极(图中用方形表示)上时,依次对控制电极5施加电压,通过使液体1往复移动能搅拌内部的成分。而且,如图11所示,即使将控制电极配置在方向不同的多条实质上的直线上,而且使该实质上的直线交叉,通过在两个不同方向反复使液体1往复移动,也能进行搅拌。这时,通过在不同方向输送液体,使液体的一部分变形,促进了扩散。如图12所示,通过在二维阵列状配置的控制电极上向沿液体1的移动方向的控制电极施加电压,也能二维地控制液体1的移动方向并进行搅拌。例如,即使像画圆那样移动液体1也能进行搅拌。这种情况,在液体以画圆的方式移动期间,液体的各部分变形,促进了扩散。这时,若油滴2的尺寸较大,则液体1在油和气体的气液界面不接触的状态在油滴的内部移动,能更快地搅拌。Next, the procedure for stirring the liquid component surrounded by oil droplets is shown. FIG. 10 shows an arrangement diagram of control electrodes for stirring the
如本实施例那样,通过用油滴包围搅拌的液体,即使为了搅拌而移动液体,由于由此产生的油的流动不传递给其它液体,所以能稳定地控制搅拌着的液体以外的液体。通过在以上的油滴中进行使合体和搅拌合并的混合操作,不会把因混合操作产生的油的流动传递给其它液体,能稳定而独立地操作液体输送器件内的许多液体。这样的混合操作在分析中是重要的,例如,为了测定作为测定血液中所含的总蛋白量的生物化学分析项目的总蛋白(TP-Total Protein)项目,通过在试样中混合1μL血液,在试剂中混合10μL第一化学药品株式会社制ォ一トセラTP试剂,测定10分钟后的吸光度就能求出。As in the present embodiment, by surrounding the stirring liquid with oil droplets, even if the liquid is moved for stirring, the flow of the oil is not transmitted to other liquids, so it is possible to stably control liquids other than the stirring liquid. By performing the mixing operation of merging and stirring in the above oil droplets, the flow of oil generated by the mixing operation is not transmitted to other liquids, and many liquids in the liquid delivery device can be stably and independently operated. Such a mixing operation is important in analysis. For example, in order to measure the total protein (TP-Total Protein) item, which is a biochemical analysis item for measuring the total protein amount contained in blood, by mixing 1 μL of blood in the sample, It can be obtained by mixing 10 μL of Otocella TP reagent manufactured by Daiichi Chemicals Co., Ltd. with the reagent, and measuring the
实施例3Example 3
本实施例表示把被油滴2包围的一个液体1分离成被油滴2包围的两个液体1的顺序。This embodiment shows the sequence of separating one
在如图13(a)那样以直线状配置的控制电极5上配置被油滴2包围的液体1时,如图13(b)所示液体1的一部分重叠,而且,对位于液体1的中心附近的控制电极5c,以及与位于液体中心附近的控制电极相邻、相对该控制电极处于对称位置的控制电极5b和5d同时或实质上同时施加电压。这样一来,如图13(c)那样液体横向变长地变形。接着,切断位于液体的中心附近的控制电极5c的施加电压。这样,如图13(d)所示,分离成两个液体(液滴)1a、1b。这时,对向着控制电极列的一个端部侧的方向比控制电极5b先配置的控制电极5a及向着控制电极列的另一个端部侧的方向比控制电极5d先配置的控制电极5e的每个施加电压,通过切断控制电极5b和5d的施加电压,如图13(e)所示,就能分离为被油滴2a包围的液体(液滴)1a和被油滴2b包围的液体(液滴)1b。如本实施例所示,通过在油滴中分离两个液体,因分离操作产生的油流动不会对分离液体以外的液体产生影响,能稳定而独立地操作液体输送器件内的许多液体。When the liquid 1 surrounded by
实施例4Example 4
本实施例表示在液体输送器件内生成被油滴2a包围的液体的顺序。This example shows the sequence of generating liquid surrounded by
如图14(a)那样在以直线状配置的控制电极5上单独配置液体1和油滴2。这里,在多个控制电极列中,从液体1的中心所处的电极看,对在向油滴2的中心所处的电极的方向配置的控制电极5b施加电压时,如图14(b)那样液体1移动到控制电极5b上。接着,如图14(c)所示,对从作为液体1的移动目的地的控制电极看在向着处于油滴2的中心的电极的方向配置的、且从处于油滴2中心的电极看在向着处于液体1的中心的电极的方向所配置的控制电极5c施加电压,切断向控制电极5b的施加电压。这时,液滴1与油滴2接触后,油滴2如图14(d)那样移动,包围整个液体1,能生成被油滴包围的液体1。如本实施例所示,通过在液体输送器件内输送液体,并使其与油接触,可以很容易地生成被油滴包围的液体。例如,在用液体输送器件进行分析的时候,通过在液体输送器件内,把试样分离成多个像本实施例那样的液体,并分别进行测定,就能同时测定许多项目,具有提高效率的效果。The
根据物理的范围或表面的亲水性、疏水性的状态,表示从蓄积在液体输送器件的一部分中的油缓冲器生成被油滴包围的液体(液滴)的顺序。在如图15(a)那样实质上以直线状配置的控制电极5a、5b、5c、5d、5e、5f上单独地配置液体1和作为油池形成的油区域11时,对控制电极5b施加电压时,液体1就如图15(b)那样移动到控制电极5b上。这时,液体1的一部分和油区域11的所在的区域重叠。接着如图15(c)那样对控制电极5c施加电压,切断向控制电极5b的施加电压。于是,液体1就移动到控制电极5c上,完全包围在液体区域11中,随后如图15(d)那样对控制电极5d施加电压,于是就移动到控制电极5d上。According to the physical range or the state of hydrophilicity and hydrophobicity of the surface, it shows the order in which the liquid (droplet) surrounded by oil droplets is generated from the oil buffer accumulated in a part of the liquid transport device. When the
接着,如图15(e)那样对控制电极5e施加电压,切断控制电极5d的电压。于是就往油区域11的外侧移动液体1。这时,油的一部分虽还与油区域11接触,但通过图15(f)那样进一步对控制电极5f施加电压,切断控制电极5e的电压,从而使一定量的油从油区域11分离,就可以生成被油滴2包围的液体1。另外,通过油区域11的范围及亲水性、疏水性的表面状态,及电极形状等的最佳化,可以从油区域分离油并能更容易地生成。如本实施例所示,通过往蓄积油的油区域输送液体并使其接触,可以很容易地生成被油包围的液体。通过接连不断地往油区域输送液体,可以使用一个油区域生成多个被油包围的液体。Next, as shown in Fig. 15(e), a voltage is applied to the
实施例5Example 5
本实施例表示将液体输送器件应用到分析系统中,把试样和试剂作为粒状的液体、即作为液滴分别导入到液体输送器件内的一个区域,作为由以输送用液体即油滴包围的油滴和试样或者由油滴和试剂等构成的复合液滴进行输送,使复合液滴合体并作为反应液,进行搅拌、检测后,直到与包围其周围的油滴一起排出的顺序。This embodiment shows that the liquid delivery device is applied to the analysis system, and the sample and the reagent are respectively introduced into a region in the liquid delivery device as a granular liquid, that is, as a droplet, as a region surrounded by a delivery liquid, that is, an oil droplet. Oil droplets and samples or composite droplets composed of oil droplets and reagents are transported, the composite droplets are combined and used as a reaction solution, stirred, detected, and discharged together with surrounding oil droplets.
图16表示分析系统的结构。分析系统具有以下各部分:液体输送器件10,用于将试样21分注到液体输送器件10内的试样单元12,用于将容纳在试剂槽中的试剂25分注液体输送器件10内的试剂单元13,用于对容纳在试样槽中的试样21的检测、例如测定试样21的内部成分的检测单元14和用于排出试样21及试剂25及油滴2的排出单元15。在试样单元12中配置有试样21、油22,能分别用试样测管16、油测管17从一个区域即试样导入口23导入到液体输送器件10内。Fig. 16 shows the structure of the analysis system. The analysis system has the following parts: a
在试剂单元13中配置有试剂25、油22,能分别用试剂测管18、油测管17从一个区域即试剂导入口24导入到液体输送器件10内。
检测单元14与在连接试样等导入部和排出部的液体输送通道的至少一部上所设置的测定部邻接地设置。The
排出单元15设有输送装置19和废液槽27,由检测单元检测的液体用输送装置19从排出口26向废液槽27排出。The
开始,在试样单元12中,从油测管17把容纳在油槽中的油22对试样导入口23供给一定量后,通过将一定量的试样21吸入到试样测管16中,将吸入的试样21从试样导入口23往液体输送器件10内送出一定量,由此分注试样21。这样,分注的一定量的油和分注的一定量的试样相对应地设置在液体输送器件10内。这时,由于往试样导入口23供给油后导入试样,从而可以使试样不附着在液体输送器件表面地导入。另一方面,在试剂单元13中也同样地从油测管17将一定量的油22供给试剂导入口24后,从试剂分配器18送出一定量的试剂25,分注试剂25。这样,分注的一定量的油和分注的一定量的试剂相对应地设置在液体输送器件10内。另外,与试样同样,由于将油供给试剂导入口24后导入试剂,因而可以使试样不附着在液体输送器件表面地导入。分注在液体输送器件10内的试样21及试剂25,在液体输送器件10内部分别输送,用检测单元14进行检测,利用排出单元15的输送装置19从排出口26抽吸,并排出到废液槽27内。Initially, in the
图17表示在液体输送器件10内操作流程的例子。在液体输送器件10内,首先,从试样导入口23分注试样21,从试剂导入口24分注试剂25后,混合已分注的试样21和已分注的试剂25成为反应液31后,测定反应液31的吸光度,最终从排出口排出反应液31。FIG. 17 shows an example of the flow of operations within the
图18表示进行液体输送器件10内的各操作的各部配置图。在液体输送器件10内,与图17的各操作相对应,存在导入试样21的试样导入部108,导入试剂25的试剂导入部109,使试样21和试剂25合体并搅拌成反应液31的混合部29,用于测定反应液31的测定部30,排出反应液31的排出部110等的各部,各部以图17的操作流程的顺序配置在液体输送器件10内,各部之间用液体输送通道28连接。在液体输送通道28、试样导入部108、试剂导入部109、混合部29、测定部30及排出部110的各个至少一个部上配置控制电极,通过控制向控制电极的施加电压,可以控制试样和试剂等液体的输送和分析。在液体输送通道的至少一部分上设置测定部30。从试样导入部108已分注的试样21通过液体输送通道28输送,与同样地从试剂导入部109分注并输送来的试剂25在混合部29混合,成为反应液31,通过液体输送通道28输送,在测定部30测定成分后,经输送并由排出部110排出。这样从液体的导入部到排出部,由于按照液体输送器件内的各操作的顺序配置,从而可以容易地对许多试样完成多种操作。FIG. 18 is a diagram showing the arrangement of various parts for performing various operations in the
图19表示本实施例所使用的液体输送器件的外观图。本实施例把高度0.5mm衬垫32夹在二片上下基片8、9之间,保持一定间隔地固定。在用油充满内部的液体输送器件的情况下,侧面虽有必要密封,以使其不漏出油,但在本实施例中,由于用以空气分开的油滴包围液体进行输送,没有必要将侧面做成使其不漏油,液体输送器件的安装变得简易。Fig. 19 shows an external view of the liquid transport device used in this example. In this embodiment, spacers 32 with a height of 0.5 mm are sandwiched between two upper and
图20表示在液体输送器件10内用于操作液体1的电压控制装置101的结构。本控制装置设置在图16所示的分析系统中,并具有控制用的计算机102和用于向液体输送器件10内预定的电极施加由控制用的计算机102控制的施加电压的联络部103。将CRT、打印机、电源与控制用的计算机102连接。控制用的计算机102具备:用于输入有关分析对象和液体输送方法的适当条件的输入部,存储与各种液体输送方法相对应的电压控制图案的电压控制图案存储部,根据从输入部输入的信息决定与分析对象相对应的电压控制图案的组合的电压控制图案调整部,对液体输送器件10施加与由电压控制图案调整部所决定的电压控制图案的组合相对应的电压的电压施加控制部。联络部103与控制电极5连接,在控制液体1时,根据从输入部输入的信息,通过联络部103把接受电压施加控制部控制的电压施加在预定的电极上。FIG. 20 shows the structure of the voltage control means 101 for operating the
图21表示试样导入部108的断面结构图。在上侧基片9的试样导入口23上以能上下移动的方式分别设置着用于导入容纳在容器中的油22的油测管17和用于分注容纳在容器中的试样21的试样测管16。对于试剂导入部109,除了把试样测管16置换成用于分注容纳在容器中的试剂25的试剂测管18以外,也能可以做成与图21同样的结构。试样测管16在与分开地分注到试样导入部108上的油滴2接触时,将试样分开地分注到油滴2的内部。因此,能可靠地将试样试样在油滴中。FIG. 21 shows a cross-sectional configuration diagram of the
进而,也可以在试样测管16外侧的至少一部分涂布疏水膜等,以给与亲油性。这时,使油22和试样测管16的亲和性良好,能更可靠地将试样21送出到油滴2内。Furthermore, a hydrophobic film or the like may be applied to at least a part of the outer side of the
这里,虽然图示了将一个试样21作为一个液滴送出到一个油滴2的内部的结构,但在送出一个液滴后通过向控制电极5施加电压使该液滴移动,就能进一步将一个以上的试样21的液滴送出到油滴2的内部。这时,就能在对作为送出对象的油滴2以外的液体的设置在输送器件内的液体不会产生影响的情况下进行液体分注。因此,也可能生成如图8所示的在一个油滴中存在许多液体的情况。Here, although the structure in which one
另外,也可以做成如下的结构,即,如图22那样,准备容纳有油22的容器22’及容纳有试样21的容器21’,首先,如图22(a)那样用测管16’从容器22’抽吸油22后,通过如图22(b)那样从容器21’抽吸试样21,从而将试样21包围在被抽吸而存储在测管16内的油22中,再如图22(c)那样把每个油22送出并分注到液体输送器件10内。这样一来,作为用于分注到液体输送器件中的结构,就没有必要设置试样测管和油测管这两种测管,从而能使结构简化。在本发明的结构中,通过将试样21送出到油滴2中,从而可以实现在测管通过油滴2和空气3的气液界面时,受到气液界面的表面张力引起的力,试样21不会附着在测管16上,微量试样21也能稳定地脱离并分注。另外,在试剂导入部109也能用同样的方法分注试剂25。以前,在用油22充满内部的液体输送器件10中,进行这样的分注时,虽然产生油界面的上下和因导入的液体引起的油的流动,但通过如本实施例那样用分开的油滴包围液体周围,则可以对液体输送器件内的其它液体不产生影响地进行分注。In addition, it is also possible to make the following structure, that is, as shown in FIG. 22, prepare the container 22' containing the
另外,在本实施例中,在试剂导入部108的油22的供给虽用油测管17,但也可以用流动池把被油22包围的试样21分注到液体输送器件10中。图23表示使用了流动池情况的试剂导入部的断面结构。在试剂导入部109也能用同样的方法分注试剂25。试样测管16和油测管17与流动池33连接,流动池测管34从流动池33延伸到液体输送器件10。开始将一定量的试样21送出到流动池内后,通过使油22流动到试样测管16的周围来分离一定量试样21,通过把每个油22挤压到液体输送器件10内,便分注了被油滴2包围的试样21。通过做成这样的结构,可以使试样以与油接触的状态把液体分注到液体输送器件10内。In addition, in this embodiment, the
另外,也可以如图29那样用阀112供给油22。这时,可以缩短抽吸油的时间,在接连不断地分注试样时,与供给油的时间缩短有关,能提高效率。供给油时,将阀的B侧和C侧连通,用注射器111把油贮积在注射器内。接着,如图29(a)那样将阀的A侧和B侧连通,用注射器111抽吸试样21。如图29(b)那样用注射器111把试样21导入到液体输送器件10内,便能分注试样21。即,具有阀和注射器的送液部在抽吸油之后抽吸试样,然后送出被油包围的试样,并将作为被油包围的试样导入到液体输送器件10内。在试剂导入部109也可以用同样的方法分注试剂25。Alternatively, the
在混合部29利用实施例2所示的方法,进行试样21和试剂25的合体及搅拌。若使用本实施例,不会把因混合多个液体产生的油的流动传递给进行混合的液体以外的其它液体,能在液体输送器件内稳定而独立地操作许多液体。In the
图24表示检测单元14和测定部30的结构。本实施例使用LED35测定吸光度。用照射透镜37把从LED35发射的光36入射到反应液31,用发光二极管38检测透过光。本实施例虽使用LED35,但如图25那样也可以使用卤灯39,用照射透镜37把由照射光纤40导入的光36照射到测定部30,用聚光透镜41把透过光聚光在聚光光纤42上,用具有分光部件的检测系统43把光分光成必要的波长来进行检测。另外,本实施例在测定部虽用光进行测定,但也可以利用电极测定液体或油滴的阻抗、和配置具有离子感应膜的电极,电测定液体内部的成分。FIG. 24 shows configurations of the
在用油充满液体输送器件内的情况下,当由导入口和排出口进入气泡时,虽然考虑了气泡和液体接触,影响液体的输送和测定的可能性,但为了从油中除掉气泡,由于使气泡与油和空气的界面接触,因而可以设想通过从液体输送器件除掉全部油再一次加入油来除掉气泡。如本实施例那样通过用油滴包围液体,则能使气泡很容易地与油和空气的界面接触,可以从油中除掉气泡。因此,也可以在测定中进行稳定的测定。In the case of filling the liquid delivery device with oil, when air bubbles enter from the inlet and outlet, although the possibility that the air bubbles will contact the liquid and affect the delivery and measurement of the liquid is considered, in order to remove the air bubbles from the oil, Since the air bubbles are brought into contact with the interface of oil and air, it is conceivable to remove the air bubbles by removing all the oil from the liquid delivery device and adding oil again. By surrounding the liquid with oil droplets as in the present embodiment, the air bubbles can be easily brought into contact with the interface between the oil and air, and the air bubbles can be removed from the oil. Therefore, stable measurement can also be performed during the measurement.
图26表示排出部110的断面结构图。输送到排出口26的反应液31和油滴2被单元15的输送装置19抽吸,并排出到废液槽27。在用油充满液体输送器件内部的情况下,排出液体时,通过抽吸液体和油在油中产生流动,但如本实施例那样,通过排出被油滴包围的液体,不会因油的流动对液体输送器件内的其它液体产生影响,能稳定的操作许多液体。由于将油滴2排出在废液槽27内,并利用比重的不同将聚集的油22和反应液21分离,因而即使排出许多反应液及包围反应液的油滴,油和反应液的处理也很容易。另外,对于以前的用油充满的液体输送器件,与试样和试剂接触的油随后与流通的试样和试剂接触,通过油使试样和试剂的成分进行混合。另一方面,若使用本结构,由于能一起排出试样或试剂或反应液和与其接触的油,因而不会使使下面的试样和试剂和成分混合,能保持液体输送器件内的油清洁。FIG. 26 shows a cross-sectional configuration diagram of the
排出即使不配置排出口及输送装置19,也可以从器件侧面或底面排出。图27表示其一个例子。在下侧基片8上设有倾斜面,将液体输送到有倾斜面的排出口排出,然后一边受到重力的辅助作用,一边排出到在下部配置的废液槽。这时,也可以将废液槽与地面连接,用电场力排出到废液槽侧。在以前的用油充满液体输送器件的内部的情况下,将侧面密封以使其不漏油,可以认为这种情况要排出液体1是困难的,但若使用本结构,没有必要将侧面或底面做成不漏油,因而能从侧面或底面排出液体,排出部的结变得简易。Discharge Even if the discharge port and the conveying
根据本实施例的结构,通过把试样及试剂包围在油滴中分别进行输送,能在液体输送器件内对许多液体进行稳定的操作。另外,在本实施例虽以向分析系统的应用为目的,但通过分别把从排出口排出的反应液及油分别加入到各自的容器中,当然也能适用于在液体输送器件内使许多液体反应生成的反应系统、和生成许多液体的混合物的混合系统中。According to the structure of this embodiment, by enclosing the sample and the reagent in oil droplets and transporting them separately, it is possible to stably handle many liquids in the liquid transport device. In addition, although the application to the analysis system is aimed at the present embodiment, it is of course also applicable to the use of many liquids in the liquid transport device by adding the reaction liquid and the oil discharged from the discharge port to their respective containers. In the reaction system formed by the reaction, and in the mixing system producing a mixture of many liquids.
实施例6Example 6
本实施例说明连接多个液体输送器件的方法。通过使用侧面不密封的液体输送器件,从而可将多个液体输送器件组合成为一个液体输送器件使用。图28表示组合两个液体输送器件的例子。液体输送器件的侧面对外敞开,通过在液体输送器件侧面用粘结剂44连接多个液体输送器件10a和10b。粘接剂44虽使用硅类粘接剂,但也可以用特氟隆(注册商标)类的疏水膜等使液体输送器件相互间接触。在使用特氟隆(注册商标)类的疏水膜的情况下,由于不必要粘接,所以在连接液体输送器件后能容易分离。并且,其配置使得各个液体输送器件内的输送通道,在连接器件时作为一个液体输送通道发挥作用。试样从试样导入口23导入到液体输送器件10a内,在混合部29a与从试剂导入口24a导入的试剂混合,通过液体输送通道28输送,在液体输送器件10b中移动。在液体输送器件10b中用混合部29b与从试剂导入口24b导入的试剂混合,从排出口26排出。这样,可以在多个液体输送器件之间输送液体,当与多个试剂反应和进行多种操作时,通过连接液体输送器件,可以配置多个进行操作的各部。另外,在独立地操作许多液体时,虽然也可以在一个液体输送器件中具有多个液体输送通道,但也可以使用液体输送器件把许多液体分配给多个液体输送器件,在各自的液体输送器件中进行操作。以前,由于用油充满的液体输送器件内部密封了侧面,因而连接液体输送器件相互间是困难的,但若使用本发明,由于没有必要密封侧面以使其不漏油,因而很容易连接多个液体输送器件。如本实施例那样,若能连接多个液体输送器件,就能将液体输送器件应用到独立地对许多液体进行多种操作的分析系统和反应系统、混合系统中。This example illustrates a method of connecting multiple fluid delivery devices. By using a liquid delivery device with an unsealed side, multiple liquid delivery devices can be combined into one liquid delivery device. Figure 28 shows an example of combining two liquid delivery devices. The sides of the liquid delivery device are open to the outside, and a plurality of
实施例7Example 7
图30表示的是将油导入口113分别设置在与试样导入口23和试剂导入口24不同之处,并从各自的口导入到液体输送器件10中,在液体输送器件10内输送试样21的液体并使其与油接触的分析系统。根据本结构,容易生成被油包围的液体。FIG. 30 shows that the
图31表示试样导入部的断面图。试样21用试样测管16抽吸,从试样导入口23分注。油22用油测管17抽吸,从油导入口113分注。被分别导入的试样21和油22在液体输送器件10内位于配置了电极的电极上。处于电极上的试样21和油22按照实施例4所示的顺序、即由图14和图15表示的顺序至少输送试样的液滴和油滴的任何一种,能生成被油包围的液体(液滴)。例如,从试样导入部沿配置了控制电极的液体输送通道向油导入部输送分开地分注的试样21,被分开地分注到油导入部的油22的至少一部分内包,作为被油滴包围的内包的液体则可沿液体输送通道输送。Fig. 31 shows a cross-sectional view of the sample introduction unit. The
混合部、排出部的结构成可做成与实施例6相同。The structure of the mixing part and the discharge part can be made the same as that of the sixth embodiment.
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Also Published As
| Publication number | Publication date |
|---|---|
| JP2006317299A (en) | 2006-11-24 |
| CN1862260A (en) | 2006-11-15 |
| EP1722234A2 (en) | 2006-11-15 |
| EP1722234A3 (en) | 2013-12-18 |
| US20060254933A1 (en) | 2006-11-16 |
| JP4547301B2 (en) | 2010-09-22 |
| US7922885B2 (en) | 2011-04-12 |
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